Automatic Lung Cancer Segmentation in 18 FFDG PET/CT Using a Two-Stage Deep Learning Approach / 대한핵의학회잡지

Purpose@#Since accurate lung cancer segmentation is required to determine the functional volume of a tumor in [ 18 F]FDG PET/CT, we propose a two-stage U-Net architecture to enhance the performance of lung cancer segmentation using [ 18 F]FDG PET/CT. @*Methods@#The whole-body [ 18 F]FDG PET/CT scan data of 887 patients with lung cancer were retrospectively used for network training and evaluation. The ground-truth tumor volume of interest was drawn using the LifeX software. The dataset was randomly partitioned into training, validation, and test sets. Among the 887 PET/CT and VOI datasets, 730 were used to train the proposed models, 81 were used as the validation set, and the remaining 76 were used to evaluate the model. In Stage 1, the global U-net receives 3D PET/CT volume as input and extracts the preliminary tumor area, generating a 3D binary volume as output. In Stage 2, the regional U-net receives eight consecutive PET/CT slices around the slice selected by the Global U-net in Stage 1 and generates a 2D binary image as the output. @*Results@#The proposed two-stage U-Net architecture outperformed the conventional one-stage 3D U-Net in primary lung cancer segmentation. The two-stage U-Net model successfully predicted the detailed margin of the tumors, which was determined by manually drawing spherical VOIs and applying an adaptive threshold. Quantitative analysis using the Dice similarity coefficient confirmed the advantages of the two-stage U-Net. @*Conclusion@#The proposed method will be useful for reducing the time and effort required for accurate lung cancer segmentation in [ 18 F]FDG PET/CT.

Basal and Acetazolamide Brain Perfusion SPECT in Internal Carotid Artery Stenosis / 대한핵의학회잡지

Internal carotid artery (ICA) stenosis including Moyamoya disease needs revascularization when hemodynamic insufficiency is validated. Vascular reserve impairment was the key to find the indication for endarterectomy/bypass surgery in the atherosclerotic ICA stenosis and to determine the indication, treatment effect, and prognosis in Moyamoya diseases. Vascular reserve was quantitatively assessed by 1-day split-dose I-123 IMP basal/acetazolamide SPECT in Japan or by Tc-99m HMPAO SPECT in other countries using qualitative or semi-quantitative method. We summarized the development of 1-day basal/ acetazolamide brain perfusion SPECT for ICA stenosis, both quantitative and qualitative methods, and their methodological issues regarding (1) acquisition protocol; (2) qualitative assessment, either visual or deep learning-based; (3) clinical use for atherosclerotic ICA steno-occlusive diseases and mostly Moyamoya diseases; and (4) their impact on the choice of treatment options. Trials to use CT perfusion or perfusion MRI using contrast materials or arterial spin labeling were briefly discussed in their endeavor to use basal studies alone to replace acetazolamide-challenge SPECT. Theoretical and practical issues imply that basal perfusion evaluation, no matter how much sophisticated, will not disclose vascular reserve. Acetazolamide rarely causes serious adverse reactions but included fatality, and now, we need to monitor patients closely in acetazolamide-challenge studies.

Relationship of EGFR Mutation to Glucose Metabolic Activityand Asphericity of Metabolic Tumor Volumein Lung Adenocarcinoma / 대한핵의학회잡지

Purpose@#EGFR-mutation (EGFR-mt) is a major oncogenic driver mutation in lung adenocarcinoma (ADC) and is more oftenobserved in Asian population. In lung ADC, some radiomics parameters of FDG PET have been reported to be associated withEGFR-mt. Here, the associations between EGFR-mt and PET parameters, particularly asphericity (ASP), were evaluated inAsian population. @*Methods@#Lung ADC patients who underwent curative surgical resection as the first treatment were retrospectively enrolled.EGFR mutation was defined as exon 19 deletion and exon 21 point mutation and was evaluated using surgical specimens. OnFDG PET, image parameters of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesionglycolysis (TLG), and ASP were obtained. The parameters were compared between EGFR-mt and wild type (EGFR-wt) groups,and the relationships between these PET parameters and EGFR-mt were evaluated. @*Results@#A total of 64 patients (median age 66 years, M:F = 34:30) were included in the analysis, and 29 (45%) patients showedEGFR-mt. In EGFR-mt group, all the image parameters of SUVmax, MTV, TLG, and ASP were significantly lower than inEGFR-wt group (all adjusted P< 0.050). In univariable logistic regression, SUVmax (P= 0.003) and ASP (P= 0.010) weresignificant determinants for EGFR-mt, whereasMTV was not (P= 0.690). Multivariate analysis revealed that SUVmax and ASPare independent determinants for EGFR-mt, regardless of inclusion of MTV in the analysis (P< 0.05). @*Conclusion@#In Asian NSCLC/ADC patients, SUVmax, MTV, and ASP on FDG PET are significantly related to EGFR mutationstatus. Particularly, low SUVmax and ASP are independent determinants for EGFR-mt.

Perspectives in Radiomics for Personalized Medicine and Theranostics / 대한핵의학회잡지

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.

Radiomics in Oncological PET/CT: a Methodological Overview / 대한핵의학회잡지

Radiomics is a medical imaging analysis approach based on computer-vision. Metabolic radiomics in particular analyses the spatial distribution patterns of molecular metabolism on PET images. Measuring intratumoral heterogeneity via image is one of the main targets of radiomics research, and it aims to build a image-based model for better patient management. The workflow of radiomics using texture analysis follows these steps: 1) imaging (image acquisition and reconstruction); 2) preprocessing (segmentation & quantization); 3) quantification (texture matrix design & texture feature extraction); and 4) analysis (statistics and/or machine learning). The parameters or conditions at each of these steps are effect on the results. In statistical testing or modeling, problems such as multiple comparisons, dependence on other variables, and high dimensionality of small sample size data should be considered. Standardization of methodology and harmonization of image quality are one of the most important challenges with radiomics methodology. Even though there are current issues in radiomics methodology, it is expected that radiomics will be clinically useful in personalized medicine for oncology.

Perspectives in Radiomics for Personalized Medicine and Theranostics / 대한핵의학회잡지

Radiomics handles imaging biomarker from high-throughput feature extraction through complex pattern recognition that is difficult for human to process. Recent medical paradigms are rapidly changing to personalized medicine, including molecular targeted therapy, immunotherapy, and theranostics, and the importance of biomarkers for these is growing day by day. Even though biopsy continues to gold standard for tumor assessment in personalized medicine, imaging is expected to complement biopsy because it allows whole tumor evaluation, whole body evaluation, and non-invasive and repetitive evaluation. Radiomics is known as a useful method to get imaging biomarkers related to intratumor heterogeneity in molecular targeted therapy as well as one-size-fits-all therapy. It is also expected to be useful in new paradigms such as immunotherapy and somatostatin receptor (SSTR) or prostate-specific membrane antigen (PSMA)-targeted theranostics. Radiomics research should move to multimodality (CT, MR, PET, etc.), multicenter, and prospective studies from current single modality, single institution, and retrospective studies. Image-quality harmonization, intertumor heterogeneity, and integrative analysis of information from different scales are thought to be important keywords in future radiomics research. It is clear that radiomics will play an important role in personalized medicine.

Radiomics in Oncological PET/CT: a Methodological Overview / 대한핵의학회잡지

Radiomics is a medical imaging analysis approach based on computer-vision. Metabolic radiomics in particular analyses the spatial distribution patterns of molecular metabolism on PET images. Measuring intratumoral heterogeneity via image is one of the main targets of radiomics research, and it aims to build a image-based model for better patient management. The workflow of radiomics using texture analysis follows these steps: 1) imaging (image acquisition and reconstruction); 2) preprocessing (segmentation & quantization); 3) quantification (texture matrix design & texture feature extraction); and 4) analysis (statistics and/or machine learning). The parameters or conditions at each of these steps are effect on the results. In statistical testing or modeling, problems such as multiple comparisons, dependence on other variables, and high dimensionality of small sample size data should be considered. Standardization of methodology and harmonization of image quality are one of the most important challenges with radiomics methodology. Even though there are current issues in radiomics methodology, it is expected that radiomics will be clinically useful in personalized medicine for oncology.

Development of tau PET Imaging Ligands and their Utility in Preclinical and Clinical Studies / 대한핵의학회잡지

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.

Development of tau PET Imaging Ligands and their Utility in Preclinical and Clinical Studies / 대한핵의학회잡지

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.

Comparison of Two Different Segmentation Methods on Planar Lung Perfusion Scan with Reference to Quantitative Value on SPECT/CT / 대한핵의학회잡지

PURPOSE: Until now, there was no single standardized regional segmentation method of planar lung perfusion scan.We compared planar scan based two segmentation methods, which are frequently used in the Society of Nuclear Medicine, with reference to the lung perfusion single photon emission computed tomography (SPECT)/computed tomography (CT) derived values in lung cancer patients.METHODS: Fifty-five lung cancer patients (male:female, 37:18; age, 67.8 ± 10.7 years) were evaluated. The patients underwent planar scan and SPECT/CT after injection of technetium-99 m macroaggregated albumin (Tc-99 m-MAA). The % uptake and predicted postoperative percentage forced expiratory volume in 1 s (ppoFEV1%) derived from both posterior oblique (PO) and anterior posterior (AP) methods were compared with SPECT/CT derived parameters. Concordance analysis, paired comparison, reproducibility analysis and spearman correlation analysis were conducted.RESULTS: The % uptake derived from PO method showed higher concordance with SPECT/CT derived % uptake in every lobe compared to AP method. Both methods showed significantly different lobar distribution of%uptake compared to SPECT/CT. For the target region, ppoFEV1% measured from PO method showed higher concordance with SPECT/CT, but lower reproducibility compared to AP method. Preliminary data revealed that every method significantly correlated with actual postoperative FEV1%, with SPECT/CT showing the best correlation.CONCLUSIONS: The PO method derived values showed better concordance with SPECT/CT compared to the AP method. Both PO and AP methods showed significantly different lobar distribution compared to SPECT/CT. In clinical practice such difference according to different methods and lobes should be considered for more accurate postoperative lung function prediction.

Prognostic value of preoperative intratumoral FDG uptake heterogeneity in early stage uterine cervical cancer / 부인종양

OBJECTIVE: We investigated the prognostic value of intratumoral [18F]fluorodeoxyglucose (FDG) uptake heterogeneity (IFH) derived from positron emission tomography/computed tomography (PET/CT) in patients with cervical cancer. METHODS: Patients with uterine cervical cancer of the International Federation of Obstetrics and Gynecology (FIGO) stage IB to IIA were imaged with [18F]FDG PET/CT before radical surgery. PET/CT parameters such as maximum and average standardized uptake values (SUV(max) and SUV(avg)), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and IFH were assessed. Regression analyses were used to identify clinicopathological and imaging variables associated with progression-free survival (PFS). RESULTS: We retrospectively reviewed clinical data of 85 eligible patients. Median PFS was 32 months (range, 6 to 83 months), with recurrence observed in 14 patients (16.5%). IFH at an SUV of 2.0 was correlated with primary tumor size (p<0.001), SUV(tumor) (p<0.001), MTV(tumor) (p<0.001), TLG(tumor) (p<0.001), depth of cervical invasion (p<0.001), and negatively correlated with age (p=0.036). Tumor recurrence was significantly associated with TLG(tumor) (p<0.001), MTV(tumor) (p=0.001), SUV(LN) (p=0.004), IFH (p=0.005), SUV(tumor) (p=0.015), and FIGO stage (p=0.015). Multivariate analysis identified that IFH (p=0.028; hazard ratio, 756.997; 95% CI, 2.047 to 279,923.191) was the only independent risk factor for recurrence. The Kaplan-Meier survival graphs showed that PFS significantly differed in groups categorized based on IFH (p=0.013, log-rank test). CONCLUSION: Preoperative IFH was significantly associated with cervical cancer recurrence. [18F]FDG based heterogeneity may be a useful and potential predicator of patient recurrence before treatment.

Clinical Outcome of Remnant Thyroid Ablation with Low Dose Radioiodine in Korean Patients with Low to Intermediate-risk Thyroid Cancer

Radioiodine activity required for remnant thyroid ablation is of great concern, to avoid unnecessary exposure to radiation and minimize adverse effects. We investigated clinical outcomes of remnant thyroid ablation with a low radioiodine activity in Korean patients with low to intermediate-risk thyroid cancer. For remnant thyroid ablation, 176 patients received radioiodine of 1.1 GBq, under a standard thyroid hormone withdrawal and a low iodine diet protocol. Serum levels of thyroid stimulating hormone stimulated thyroglobulin (off-Tg) and thyroglobulin-antibody (Tg-Ab), and a post-therapy whole body scan (RxWBS) were evaluated. Completion of remnant ablation was considered when there was no visible uptake on RxWBS and undetectable off-Tg (<1.0 ng/mL). Various factors including age, off-Tg, and histopathology were analyzed to predict ablation success rates. Of 176 patients, 68.8% (n = 121) who achieved successful remnant ablation were classified into Group A, and the remaining 55 were classified into Group B. Group A presented with significantly lower off-Tg at the first radioiodine administration (pre-ablative Tg) than those of Group B (1.2 +/- 2.3 ng/mL vs. 6.2 +/- 15.2 ng/mL, P = 0.027). Pre-ablative Tg was the only significant factor related with ablation success rates. Diagnostic performances of pre-ablative Tg < 10.0 ng/mL were sensitivity of 99.1%, specificity of 14.0%, positive predictive value of 71.1%, and negative predictive value of 87.5%, respectively. Single administration of low radioiodine activity could be sufficient for remnant thyroid ablation in patients with low to intermediate-risk thyroid cancer. Pre-ablative Tg with cutoff value of 10.0 ng/mL is a promising factor to predict successful remnant ablation.